The overall goal of this project is to develop new classes of semiconducting nanocrystals (NC, or quantum dots (QD)) that will function as highly efficient, stable, biologically compatible in vivo tags for the early detection of cancer. In prior research we have developed QD and subsequently tested them for in vivo applications in cancer. While these materials have many advantages over organic fluorochromes, it has also become clear that Cd containing materials will unlikely be suited for clinical use. For these reasons we have developed novel NC materials that appear highly promising for biological applications. In addition, we are extending the functionality of these and other QD for targeted, lifetime and multimodality imaging. Many of the biologically suited materials will be based on affinity ligands attached to NC in multivalent and polyvalent forms. In essence this project will create a toolbox of highly novel, inorganic nanomaterials for this CCNE consortium. The specific aims are to 1) synthesize, characterize and functionalize a new class of biological stable NC that are based on biologically inert building blocks (GaN, InGaN, and Si), 2) synthesize and develop new types of inorganic semiconductor heterostructured NC with increased (100 ns) lifetimes and high quantum to yield more efficient in vivo diagnostics, 3) develop functional "smart" NC that will have dual functions, for example magnetic and fluorescent nanoparticles or metal and semiconductors that could be used as dynamic sensors, 4) develop nanoparticles that are functionalized with a) increased valency of biological ligands such that higher number of shorter peptides ligands can bind to the cell surface of interest, and still maintain an overall high affinity (multivalency) and b) have multiple different biological ligands attached to the same nanoparticle tag (polyvalency) and 5) test the efficacy and toxicity of newly developed nanomaterials in mouse models of cancer.